Oxidation with Cupric Acetate

OXIDATION WITH CUPRIC ACETATE Coupling of Terminal Alkynes [58] 

To a solution of 2 g (0.01 mol) of cupric acetate in 200 mL of pyridine-methanol-ether (1 1 4), 0.400 g (0.0048 mol) of 2-ethyl-3-butyn-2-ol is added, and the mixture is refluxed for 20 min. After evaporation of most of the solvent in vacuo, the residue is acidified and extracted with ether, and the extract is evaporated to give 0.350 g (88%) of 2,7-dimethylocta-3,S diyne 2,7-diol, mp 128-130 C. 

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By adding l4C-labelled sodium cyanide to L-threo-pentos-2-ulose (9), L-[l-14C]ascorbic acid was prepared (see Scheme 2) having an activity592-596 of 2.1 x 108 counts, min-1, mg-1. L-Xylose was prepared by the sequence shown in Scheme 21. The resulting L-xylose was oxidized with cupric acetate to 9 in 40-50% yield. In the second procedure, [1-14C]1 (specific activity 0.1 /iCi. mg-1) was purified by way of 5,6-O-cyclohexylidene-L-ascorbic acid.596... 

Oxidation of formazans with a wide range of oxidizing agents leads to 2,3-disubstituted tetrazolium salts. Recently, oxidations with cupric acetate and cobalt chloride have led to mixtures of metal-formazan complexes and tetrazolium salts arising from competing reactions in which the balance depended on the substituents present in the formazans.462 Reduction of 1,4,5-trisubstituted tetrazolium iodides with NaBH has been used to prepare A2-tetrazolines.463 A similar attempted reduction of 1,3,5-trisubstituted tetrazolium salts gave no reaction.463... 

Koshiishi and Imanari (42) used the postcolunm ascorbic acid oxidation with cupric acetate to DHA and o-phenylenediamine for derivatization. Ascorbic acid and DHA were assessed in a single run (Fig. 6). Their system consisted of a double-plunger pump for pumping o-phenylenediamine and cupric acetate for postcolumn reactions. The fluorescence detector was set at exitation wavelength of 345 nm and emission wavelength of 410 nm. They introduced the poly(ethyl-ene glycol) copolymer as separation material in the analytical column (see Sect. III.C). 

A solution of bismuth trioxide in hot glacial acetic acid provides a specific method for the oxidation of acyloins. " The reaction rate is dependent on the steric accessibility of the ketol system. A 2,3-ketol requires less than one hour for completion but an 11,12-ketol is not yet fully oxidized in thirty hours." The reaction is highly selective as a-keto acids, hydrazines and phenols are not oxidized. In a direct comparison with cupric acetate, this procedure is somewhat superior for the preparation of a 2,3-diketone from a 2-keto-3-hydroxy steroid. ... 

Oxidative addition consumes one equivalent of expensive Pd(OAc)2 in most cases. However, progress has been made towards the catalytic oxidative addition pathway. Knolker s group described one of the first oxidative cyclizations using catalytic Pd(OAc)2 in the synthesis of indoles [19]. They reoxidized Pd(0) to Pd(II) with cupric acetate similar to the Wacker reaction, making the reaction catalytic with respect to palladium [20]. 

Oxidative coupling, phenylacetylene to. diphenyldiacetylene with cupric acetate, 46,39... 

A more-direct method of preparation is oxidation of aldoses, and optimal yields are afforded by the action of cupric acetate in methanol or ethanol.417 This method is suitable for large-scale preparation of intermediates however, a pure product is obtained only by chromatographic separation from the unreacted sugar byproducts. The synthesis of D-eryt/wo-pentos-2-ulose and its D-threo isomer by oxidation of D-arabinose and D-xylose, respectively, with cupric acetate followed by anion-exchange chromatography has been reported.418 The only product obtained by oxidation of D-glucose with sodium 2-anthraquinonesulfonate in alkaline... 

Oxidation of JV-hydroxypiperidine with cupric acetate or potassium ferricyanide gives J1-piperideine 1-oxide (30) in addition to a dimer or trimer.184,185 Dehydrogenation of l-hydroxy-2-phenylpiperidine takes a similar course.189... 

Cupric acetate is also used for oxidations of acyloins. Diphenylacetoin is converted almost quantitatively into dibenzylglyoxal when refluxed with cupric acetate in 70% acetic acid for 7 min [353]. Sebacoin (2-hydroxy-cyclodecanone) gives sebacil in 88-89% (equation 449) yield [359]. 

This Cl homologation of osones proved to be valuable in the preparation of L-ascorbic acid analogues (16) as well as in the preparation of radiolabeled L-ascorbic acid (17-20), This synthesis was greatly improved when aldoses were discovered to be directly oxidized to osones with cupric acetate (Equation 1) (21), Subsequently, the conditions were modified so that D-xylose could be oxidized to D-xylosone in 50-55% yield with cupric acetate in methanol. The intermediacy of the imino ether was proved by the isolation of 7 when D-glucosone was treated with potassium cyanide (16), The initial cyanohydrin adduct (3a) easily undergoes cyclization to the imino ether intermediate (aqueous solution for 10 min at room temperature. Scheme 5). This feature will be compared with the conditions required for the lactonization of other intermediates. 

NH4OH gave 9. Oxidation of 9 with cupric acetate afforded 5-deoxy-L-arabinosone 10, followed by reaction with acetone oxime and 5% NH4OH to produce the a-keto aldoxime 11. Reaction of 11 with EtOCOCH(NH2)CN in ethanol afforded 12, which was treated with sodium methoxide and guanidine hydrochloride to afford 13. Reduction with sodium dithionite in aqueous solution buffered to pH 7 gave L-eryt/iro-biopterin (2). 

A final interesting finding in this area is that oxidation of 2.3.8 with cupric acetate gave the diketo derivative 2.3.18, and treatment of this with hydrazine gave the pyrazoline 2.3.19, which is claimed to be an antitumor agent (54). 

Catalytic oxidation of sugars and alcohols is a more direct method. Hydrogen peroxide and iron salts were used originally (see under Hydrogen peroxide oxidations). However, much better yields have been obtained by the direct oxidation with cupric salts 159). The action of a limited excess of cupric acetate for a short time on methanol solutions of L-sorbose or l-xylose has given a 60 % yield of the osone. 

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